Section 2 pathogenic mechanism of infectious diseases and immunity against infection

1. Section 2pathogenic mechanism of infectious diseases and immunity against infection 《感染性疾病》

2. Main content Bacterial infection 1. pathogenic mechanism 2. immunity against bacterial infection 3. types of infection Virus infection 1. pathogenic mechanism 2. immunity against virus infection 3. types of infection Fungus infection

3. pathogenic mechanism of bacterium

4. bacterial virulence invaded bacterial number invaded pathway Three determined factors for bacterial pathogenicity:

5. Flagellum: Adhesin: including pili and LTA, as well as biofilm form Adhesion and colonization： Invasive enzymes: Invasin---type 3 secretion system--- cytoskeleton rear- rangements---internalization invasiveness Invasiving： Bacterial virulence Anti-phagocytosisi: capsule IgA enzyme: Antigen variation Immune escape: Exotoxin Endotoxin toxin

6. Ⅰ. bacterial virulence 1. invasiveness (1)flagellum (2)adhensin a. pili adhesin: b. non-pili adhesin 1) Adhesion and colonization： See table 1

7. Bacterial adhesion

8. Table 1. bacterial adhesin and its receptor 产生菌 靶细胞受体

9. (biofilm) 3.细菌生物被膜 （bacterial biofilm）

10. Biofilm forming on the surface of ductus venosus by staphylococcus, SEM×6000（From Lansing M.Prescott et al. Microbiology, 5th Edition, McGraw-Hill Companies; 2002: p920）

11. 2) invasing： (1) invasive enzymes: hyaluronidase, streptokinase, IgA clastic enzyme

12. (2) invasin: Invasin type 3 secretion system cytoskeleton rearrangements internalization apoptosis Ipa: invasion plasmid antigen Shigella bacteris

13. 3) Immune escape: Anti-phagocytosisi: capsule IgA enzyme: Antigen variation

14. 2. toxin (1)exotoxin produced by G＋and few G－ bacteria a. Main characteristic： protein high toxicity heat labile highly antigenic, toxoid after detoxication b. claasification： neurotoxin cytotoxin enterotoxin

15. Type A-B toxin for example: cholera toxin

17. (2) endotoxin G－bacteria LPS, within the outer membrane a. components： O specific polysaccharide core polysaccharide lipid A b. Main characteristic： relative weaker toxicity heat stable without toxoid febrile reaction

18. + 内毒素休克 activation mechanisms of endotoxin

19. characteristics of exotoxin and endotoxin 区别要点 外毒素 内毒素 来源 革兰阳性菌及部分革兰阴性 革兰阴性菌细胞壁 菌细胞产生向 外分泌或菌体 裂解后释放 溶解后释放 化学成份 蛋白质 脂多糖 稳定性 不稳定，加热60℃以上稳定， 160℃ 迅速破坏 2-4h才被破坏 抗原性 抗原性强，刺激机体产生 高浓抗毒素;可经甲醛 较弱，不能经甲醛 脱毒制成类毒素 脱毒制成类毒素 毒性作用 强，对组织器官有选择性 较弱，各种细菌内毒 毒害作用， 引起特殊的 素的毒性作用大致相 临床表现 同，引起发热、白 细胞变化、休克、DIC等

20. Immunity against bacterial infection Ⅰ. Innate immunity： 1. distinguishing feature: a. inherited b. “first line” of defense against infection c. nonspecific 2. constituent：

21. (1) Biological barriers: including: skin, mucous membranes, blood-brain, blood-placenta activity：mechanic blocking; secretion of bacteriocidal substance antagonistic effect by normal flora

22. (2) Phagocytosis: macrophage (monocyte & lymphocytes) neutrophils The process of phagocytosis: a. migration: through chemokine b. recognition: by PAMP and PRR (TLR) c. ingestion: to form phagosome d. killing: rely on oxygen, nitrogen

23. Process of phagocytosis

24. Phgocytosis result: a. complete phagocytosis b. incomplete phagocytosis as well as tissue damage

25. (3) humoral factors： complement, lysozyme, β-lysin, defensin, cytokines, C-reaction protein (CRP)

26. 2. Adaptive (specific) immunity • mucosal immunity --- mediated by M cell and sIgA (2) humoral immunity --- mediated by antibodies through neutralizing and ADCC etc. (3) Cell-mediated immunity --- mediated by T lymphocytes through CTL and Th1, as well as γδT

27. CTL CD4+ Th1cell

28. Immunity against bacterial infection Ⅰ. Against extracellular bacteria mainly rely on humoral immunity - blocking adhesion and colonization - opsonazation of phagocytosis - neutralization of exotoxin - activation of complement - ADCC effect

29. Ⅱ. Against intracellular bacteria mainly rely on cell-mediated immunity a. CTL secretion of perforin apoptosis b. CD4+ Th1: secretion of IL-2, IFN-γ, TNF-β

30. Immunity against bacterial infection

31. Disemmination of bacterial infection Ⅰ. Source of infection： a. endogenous (self infection) b. exogenous Ⅱ. pathway： damaged skin and mucosal respiratory tract gastrointestinal tract sexual (STD) …

32. Type of bacterial infection Ⅰ. Inapparent infection most common, more than 90% infection Ⅱ. Apparent infection a. according to illness condition (pressing or otherwise) acute chronic subacute

33. b. According to the location and characteristics localized infection generalized infection generalized infection toxemia, endotoxemia bacteremia, septicemia, pyemia sepsis

34. pathogenic mechanism of virus

35. Including three aspects mainly: 1. Cell injury or cell level 2. Immunopathogensis or body level 3. Immune escape

36. Iceberg concept of infection

37. 1. Cell injury or cell level cell lysis steady state infection apoptosis forming inclusion body gene integration, as well as cell transformation

38. (1) Cell lysis cytopathic effect, CPE： including cell lysis or necrosis, inclusion body formation, cytoplasmic vacuolization Most common in naked virus

39. CPE

40. CPE

41. Indicator of virus replication intracellular 细胞病变(Cytopathic effect, CPE) 细胞团缩、裂解、肿胀、变圆 细胞融合或聚集成葡萄串样等 Un-infected cell infected cell

42. Vero cells infected SARS virus CPE

43. (2) Steady state infection Most common in enveloped virus Without cell lysis, but changes on cell membrane, such as emerging new antigen

44. uninfected HIV infected HIV infected (at higher magnifcation)

45. (3) Induced apoptosis

46. (4) forming inclusion body inclusion body of CMV (nucleus, cytoplasm, acid-philics)

47. Inclusion body

48. （Nigri body in cytoplasm)

49. (5) Gene integration and cell transformation a. Loss of contact inhibition b. Maybe related to tumorigenesis

50. 2. Immunopathogensis or body level (1)Tissue tropism (2) Immunopathogensis mediated by antibody type Ⅳ allergy mediated by inflammatory cytokines (3) damaged immune system